Na,K-ATPase, consisting of a- and p-subunits, is a key regulator of sodium and potassium ion homeostasis in mammalian cells. In addition to its enzyme activity, the subunits are crucial to maintain the well- differentiated phenotype of epithelial cells. Reduced p-subunit expression is associated with epithelial mesenchymal transition (EMT) that occurs during cancer development. It has been shown that increased expression of the transcription suppressor protein, Snail, is elevated in invasive and metastatic cancer cells. We have previously demonstrated that the Na,K-ATPase prsubunit is suppressed by Snail in carcinoma cells. The first specific aim of this proposal examines the molecular mechanism by which Snail suppresses the transcription of Na,K-ATPase prsubunit. In the second aim, a novel assay will be employed to identify small molecules that might up-regulate Prsubunit expression in cancer cells. These studies should reveal insights into the role of pi-subunit in normal and cancer cells. [unreadable] [unreadable] [unreadable]